Tissue cultures are used for many purposes and especially for the production of therapeutic proteins and polypeptides. Preferably, a tissue culture should define a dense mass which is uniform or at least as symmetric as possible. Thus, tissue culture systems should preferably assure that all cells receive adequate nutrition and oxygen for proper growth and each cell should receive about the same amount of oxygen and nutrient, or at least each cell of a geometrically symmetrically located pair should receive about the same amounts of oxygen and nutrients. Otherwise, some tissue necrosis will occur.
To date various systems have been used for the culture of mammalian cells. These systems have employed sponge matrices, multiple tubing, stacked-plate systems, coiled plastic films or micro-carrier suspension cultures. A device described in Ku et al, Biotech. and Bioeng., Vol. XXIII, pp. 79-85 (1981) employs a flat bed hollow-fiber cell culture system, using anisotropic tubing sandwiched between microporous filter plates. The cells attach to a hollow fiber through which a sterile CO.sub.2 -air mixture is passed. Media flow is directed normal to the plane of the fiber bed. This system, while successful, presents difficulties. Because the system lacks uniform distribution of fibers, dead spaces where insufficient nutrient or oxygen is present can arise, thus leading to tissue necrosis. Moreover, the reactors have limitations in scale in the direction of height. In a system designed by Stanford University, cells are immobilized in the walls of isotropic tubes. Gas is supplied outside the tubes while liquid is supplied in the center. In the Stanford device, large tube wall thicknesses and small porosities represent barriers to adequate gas and liquid diffusion to mammalian cells immobilized in the walls. This limits packing densities and viability of mammalian cells.